ARHGAP8
protein-codingRho GTPase activating protein 8, the group of Rho GTPase activating proteins|BCH domain containing
Gene summary
This gene encodes a member of the RHOGAP family. GAP (GTPase-activating) family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. GAP proteins alternate between an active (GTP-bound) and inactive (GDP-bound) state based on the GTP:GDP ratio in the cell. This family member is a multidomain protein that functions to promote Erk activation and cell motility. Alternative splicing results in multiple transcript variants. Read-through transcripts from the upstream proline rich 5, renal (PRR5) gene into this gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~110.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARHGAP8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_181335.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 81 | 9 | 2 | 92 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 81 | 13 | 3 | 97 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_851852.2 | 11 | MANE Select | |
| Ensembl | ENSP00000348407.6 | 11 | MANE Select | |
| RefSeq | NP_001017526.1 | 12 | Standard | |
| RefSeq | NP_001185655.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Rho GTPase cycle
- Signaling by Rho GTPases
- Regulation of RhoA activity
Biological Process
- signal transduction
- positive regulation of GTPase activity
- regulation of small GTPase mediated signal transduction
- positive regulation of ERK1 and ERK2 cascade
Molecular Function
- GTPase activator activity
- protein binding
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000389773
- Coding exons
- 15
- Length
- 160311
- Individuals with no LoFs
- 124109
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 459
- Defined
- 124569
- p
- 0.00185
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -4.19 | 562 | 344 | 1.64 | 0.0000226 | 3567 |
| Missense (PolyPhen) | 137 | 93.787 | 1.4608 | 1091 | ||
| Synonymous | -6.17 | 255 | 157 | 1.63 | 0.0000116 | 1101 |
| Loss of Function | -1.62 | 36 | 26.9 | 1.34 | 0.00000123 | 311 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00076 | 0.00074 | rare |
| Latino/Admixed American | 0.0060 | 0.0060 | notable |
| Ashkenazi Jewish | 0.0019 | 0.0019 | notable |
| East Asian | 0.0071 | 0.0070 | notable |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00057 | 0.00056 | rare |
| South Asian | 0.00078 | 0.00072 | rare |
| Other | 0.0014 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.973
- RVIS EVS
- 2.3
- RVIS percentile EVS
- 98.33
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.230